1. Field of the Invention
The present invention relates to a method for treating tau-associated diseases, particularly, to a method for treating Alzheimer's disease (AD).
2. Description of Related Art
Alzheimer's disease (AD) may cause progressive cognitive decline and memory loss, and the probability of suffering Alzheimer's disease increases with aging. With aging populations, the worldwide prevalence of AD will increase to more than 80 million by the year of 2040.
The reason and the mechanism of Alzheimer's disease remain unclear. Suggested mechanisms for the disorder include cholinergic hypothesis, amyloid hypothesis, and tau hypothesis. The most credible hypothesis is the abnormal tau aggregation. In this hypothesis, the imbalance between the catalytic activities of the kinase and phosphatase results in hyperphosphorylation of tau protein and forming the neurofibrillary tangles which disintegrate the microtubules in the neurons. Accordingly, the delivery system in the neurons will be destroyed, and resulting the death of the neurons.
Glycogen synthase kinase-3β (GSK-3β) is involved in the formation of hyperphosphorylated tau protein and is the main kinase that phosphorylates tau protein. Hence, GSK-3β can serve as a key target for treating Alzheimer's disease by inhibiting the activity of GSK-3β for alleviating tau aggregation.
Several GSK-3β inhibitors were disclosed by Phukan (2010) (Phukan et al., 2010. GSK-3β: Role in therapeutic landscape and development of modulators. Br. J. Pharmacol. 160, 1-19) which have been found and used in cell models and animal models for treating Alzheimer's disease. However, none of these GSK-3β inhibitors has passed the clinical trial for clinical therapy.
Therefore, it is desirable to provide a pharmaceutical composition which is effectively in inhibiting the activity of GSK-3β and preventing hyperphosphorylation of tau protein in neurons for treating Alzheimer's disease.